4-Bromobutyryl chloride → HCID 118115754, compound

Participants

Reaction Steps

(R)-5-(3-Aminopiperidin-1-yl)-3-(4-(1-cyclopentylpiperidin-4-yl)phenylamino)pyrazine-2-carboxamide (436) (50 mg, 0.1 mmol) was dissolved in 4 mL DMF. To it were added DIEA (180 μL, 1.0 mmol) and then 4-bromobutyryl chloride (56 mg, 0.3 mmol). The mixture was stirred at RT for 1.5 hours, diluted with 60 mL EtOAc, washed with water ×3, dried, concentrated in vacuo to afford crude (R)-5-(3-(4-bromobutanamido)piperidin-1-yl)-3-(4-(1-cyclopentylpiperidin-4-yl)phenylamino)pyrazine-2-carboxamide (448). It was dissolved in 3 mL dry DMF and the solution was stirred at RT. To it was added NaH (60%, 30 mg), and the mixture was stirred for 1 hour. It was quenched with 0.5 mL TFA, and directly subjected to reverse phase preparative HPLC using 5 mM HCl (aq) and nest MeCN to isolate the title compound, (R)-3-(4-(1-cyclopentylpiperidin-4-yl)phenylamino)-5-(3-(2-oxopyrrolidin-1-yl)piperidin-1-yl)pyrazine-2-carboxamide (449), as HCl salt (7 mg). LC-MS (ESI): m/z (M+1) 532.6. UV: λ=267, 275, 305, 335, 373 nm.

Provenance & Evidence